Interaction Study of Different Forms of Human Recombinant Anti-Mullerian Hormone with a Chimeric Analogue of the AMH Type II Receptor

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2021-08-16 DOI:10.1134/S1990750821030082

A. Ya. Rak, A. V. Trofimov, A. M. Ischenko, A. V. Sokolov

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引用次数: 0

Abstract—

Anti-mullerian hormone (AMH), a homodimeric glycoprotein, described over 70 years ago by A. Jost, is the least studied member of the transforming growth factor beta superfamily. Despite the antitumor activity of AMH discovered at the end of the last century, creation of effective AMH-based drugs is hampered primarily by the lack of information on the mechanism of interaction of various AMH forms with a specific type II receptor (MISRII). Previously, we have shown that not only the full-length activated hormone but also its C-terminal fragment (C-rAMH) could bind to MISRII. In this work, using the surface plasmon resonance technique, we have compared the interaction of three forms of recombinant AMH (rAMH) with the MISRII analogue—the chimeric protein MISRII-Fc containing AMH type II receptor and-Fc fragment of the human IgG1 heavy chain. Comparison of the binding of MISRII-Fc, immobilized on a chip with group specificity for human immunoglobulins, to C-rAMH, to intact rAMH (pro-rAMH), and to rAMH containing one uncleaved monomer (hc-rAMH), showed that the K_D of the complexes increased: 1.7 nM, 88 nM and 110 nM, respectively. Thus, we have shown that the C-terminal fragment of AMH exhibits the maximum affinity for the recombinant MISRII analogue, thus indicating the prospects for the development of drugs based on this hormone derivative.

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不同形式的人重组抗苗勒管激素与AMH II型受体嵌合类似物的相互作用研究

摘要:抗苗勒管激素(AMH)是一种同源二聚体糖蛋白，由a . Jost在70多年前描述，是转化生长因子β超家族中研究最少的成员。尽管在上世纪末发现了AMH的抗肿瘤活性，但由于缺乏各种AMH形式与特定II型受体(MISRII)相互作用机制的信息，阻碍了基于AMH的有效药物的开发。之前，我们已经证明，不仅全长激活激素，而且其c端片段(C-rAMH)也可以与MISRII结合。在这项工作中，我们使用表面等离子体共振技术，比较了三种形式的重组AMH (rAMH)与MISRII类似物(含有AMH II型受体和人类IgG1重链fc片段的嵌合蛋白MISRII- fc)的相互作用。将固定在人免疫球蛋白组特异性芯片上的MISRII-Fc与C-rAMH、完整rAMH (pro-rAMH)和含有一个未裂解单体的rAMH (hc-rAMH)的结合比较显示，复合物的KD分别增加了1.7 nM、88 nM和110 nM。因此，我们已经证明AMH的c端片段对重组MISRII类似物具有最大的亲和力，从而表明基于该激素衍生物的药物开发前景。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.